Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 602185, 10 pages http://dx.doi.org/10.1155/2014/602185

Research Article Recombinant Lysostaphin Protects Mice from Methicillin-Resistant Staphylococcus aureus Pneumonia Chen Chen,1,2,3,4 Huahao Fan,1,5 Yong Huang,1 Fan Peng,1 Hang Fan,1 Shoujun Yuan,2 and Yigang Tong1 1

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China 2 Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850, China 3 Anhui Medical University, Hefei 230032, China 4 Laboratory of Gene Regulation, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan 5 Department of Microbiology, Peking University Health Science Center, Beijing 100191, China Correspondence should be addressed to Shoujun Yuan; [email protected] and Yigang Tong; [email protected] Received 20 February 2014; Accepted 18 June 2014; Published 16 July 2014 Academic Editor: Ranadhir Chakraborty Copyright © 2014 Chen Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The advent of methicillin-resistant Staphylococcus aureus (MRSA) and the frequent and excessive abuse of ventilators have made MRSA pneumonia an inordinate threat to human health. Appropriate antibacterial therapies are crucial, including the use of lysostaphin as an alternative to antibiotics. To explore the potential use of lysostaphin as a therapeutic agent for MRSA pneumonia, mice were intranasally infected with MRSA and then treated with recombinant lysostaphin (rLys; 45 mg/kg in the high-dose group and 1 mg/kg in the low-dose group) (0.33 mg/mL, 15 mg/mL), vancomycin (120 mg/kg) (40 mg/mL), or phosphate-buffered saline (PBS, negative control) 4 h after infection. Therapeutic efficacy was assessed by mouse survival, lung histopathology, bacterial density in the lungs, bodyweight, lung weight, temperature, white blood cells counts, lymphocytes counts, granulocytes counts, and monocytes counts. The mice treated with rLys showed lower mortality, less lung parenchymal damage, and lower bacterial density at metastatic tissue sites than mice treated with PBS or vancomycin. The overall mortality was 100%, 60%, 40%, and 60% for the control, vancomycin, high-dose rLys, and low-dose rLys groups, respectively. These findings indicate that, as a therapeutic agent for MRSA pneumonia, lysostaphin exerts profound protective effects in mice against the morbidity and mortality associated with S. aureus pneumonia.

1. Introduction Staphylococcus aureus is one of the most common human pathogens. Up to 20–30% of carriers are persistently and asymptomatically colonized and 50–60% are intermittently colonized [1]. Staphylococcus aureus causes many skin and soft-tissue infections and invasive diseases such as sepsis, endocarditis, pneumonia, and osteomyelitis [2]. These infections are complex to treat because this bacterial species can become resistant to antibiotics. At present, methicillinresistant S. aureus (MRSA) is one of the most commonly identified antibiotic-resistant pathogens in many parts of

the world. Moreover, MRSA infection rates have increased exponentially worldwide over the past few decades. Most of these infections, including sepsis and pneumonia, are often characterized by fulminant onset, rapid progression, and in a subset of patients, a fatal outcome [3]. Among these invasive infections, necrotizing S. aureus pneumonia has emerged as one of the most lethal [4, 5]. The reduced efficacy of vancomycin and linezolid against MRSA has increased the threat of incurable staphylococcal infections [6]. The proportion of MRSA exceeds 10% in the 24 participant countries within the European Antimicrobial Resistance Surveillance System (EARSS) [7]. Moreover, accumulating

2

BioMed Research International

Table 1: Bacterial antibiotic susceptibility testing of MRSA strain MRSA-117. Antibiotic Amoxicillin/CA Gentamicin Imipenem Oxacillin G Penicillin-G Rifampin Tetracycline SMZCO Vancomycin Levofloxacin Azithromycin Ampicillin/sulbactam Clarithromycin Quinupristin/dalfopristin Nitrofurantoin Linezolid Moxifloxacin Tigecycline

MIC (𝜇g/mL) >=16

>=0.5 >=32 >=16 40 =8

0.5 32 2 >=8

Recombinant lysostaphin protects mice from methicillin-resistant Staphylococcus aureus pneumonia.

The advent of methicillin-resistant Staphylococcus aureus (MRSA) and the frequent and excessive abuse of ventilators have made MRSA pneumonia an inord...
1MB Sizes 0 Downloads 7 Views